The purpose of this investigation is to examin the structure of biotin enzymes by electron microscopy in conjunction with other biochemical and biophysical tools. Enzymes to be studied include pyruvate carboxylase from a number of sources and transcarboxylase from the propionic acid bacteria. These enzymes have complex quaternary structures but are sufficiently large that it is unlikely that they will be studied definitively by X-ray crystallographic methods in the near future. Methods of study will include complexing of the enzymes or the entire enzyme. These studies should help reveal the location of specific sites on the subunits and the enzyme. Cross-linking reagents will also be used to stabilize quaternary structures and to establish their interrelationships. Other enzymes, particularly those involved in the metabolism of P-enolpyruvate will be examined also by electron microscopy.